This applications claims priority of United Kingdom Patent Application GB 14 10987.0, filed Jun. 20, 2014.
The invention relates to a device and a method for the stimulation of neurons and muscle cells according to the principle of magnetic stimulation, while the invention generates substantially less acoustic sound emission for the same activation strength compared to the state of the art. This invention reduces the acoustic sound emission, usually a clicking sound, which is a safety risk in magnetic stimulation and causes undesired uncontrollable sensory-auditory brain stimulation, by increasing the frequency of a substantial portion of the spectrum of the pulse, preferably to or above the human hearing range. Furthermore, the invention relates to a quiet coil technology that reduces the conversion of electrical energy into mechanic-acoustic oscillations, whereby the transmission of the mechanic-acoustic oscillations to the surface is suppressed by elastic decoupling and the mechanic-acoustic energy is converted into heat by viscoelastic material deformation instead.
Transcranial magnetic stimulation (TMS) is a technique for non-invasive brain stimulation with strong, brief magnetic pulses that induce an electric field in the brain. TMS is widely used in the neurosciences as a tool for probing brain function. It is also an FDA-approved treatment for depression, and is under study for other psychiatric and neurological disorders. TMS has been demonstrated to enhance cognitive function in healthy subjects as well.
A TMS device includes a pulse generator and a stimulation coil that is placed on the subject's head.
Typical TMS devices generate coil current pulses that are sinusoidal with main frequency component of 1-5 kHz, current amplitude up to 8 kA, and resulting magnetic field strength on the coil surfaces up to 2.5 T. The high amplitude pulses result in electromagnetic mechanical forces within the pulse generator, the stimulation coil, and the cable connecting them. Of these, the sound of the TMS coil is dominant due to the strong magnetic field in the coil and is most difficult to suppress since the coil is placed on the subject's head, where it is conducted by air and skull bone [Nikouline V., Ruohonen J., and Ilmoniemi R. J. (1999). The role of the coil click in TMS assessed with simultaneous EEG. Clinical Neurophysiology, 110(8):1325-1328.]. The mechanical vibration produced by the forces results, in turn, in a loud click sound that may be as high as 120-140 dB 10 cm from the coil, and have peak spectral power in the 1-7 kHz range [Starck J., Rimpilainen I., Pyykko I, and Toppila E. (1996). The noise level in magnetic stimulation. Scandinavian Audiology, 25(4): 223-226; Counter S. A., Borg E. (1992) Analysis of the coil generated impulse noise in extracranial magnetic stimulation. Electroencephalography and Clinical Neurophysiology, 85(4):280-288.]. The loud noise generated by conventional devices is a significant limitation of TMS, having the following key disadvantages:
(1) The loud click noise can cause hearing damage in the TMS subject, TMS operator, and other persons or experimental animals in the vicinity of the system [Counter S. A., Borg E. (1992) Analysis of the coil generated impulse noise in extracranial magnetic stimulation. Electroencephalography and Clinical Neurophysiology, 85(4):280-288; Counter S. A., Borg E., and Lofqvist L. (1991). Acoustic trauma in extracranial magnetic brain stimulation. Electroencephalography and Clinical Neurophysiology, 78(3):173-184; Rossi S., Hallett M., Rossini P. M., and Pascual-Leone A. (2009). Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clinical Neurophysiology, 120(12):2008-2039.]. Therefore, anyone in the immediate vicinity of the TMS device is required to wear hearing protection, for example ear plugs or earphones [Rossi S., Hallett M., Rossini P. M., and Pascual-Leone A. (2009). Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clinical Neurophysiology, 120(12):2008-2039.]. Failure of the hearing protection can expose to risk of hearing loss, as exemplified by the occurrence of permanent hearing loss in a subject whose ear protection had fallen out during an rTMS session [Zangen, A., Y. Roth, et al. (2005). Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil. Clinical Neurophysiology, 116(4):775-779.]. The risk of impact on hearing may be higher in children [Rossi S., Hallett M., Rossini P. M., and Pascual-Leone A. (2009). Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clinical Neurophysiology, 120(12):2008-2039.]. This issue is exacerbated in environments where the mechanical forces are increased and/or acoustic reverberation is present, for example in magnetic resonance imaging (MRI) scanners during interleaved TMS and functional MRI (fMRI).
(2) Even with hearing protection, the auditory perception of the TMS sound is substantial and often unpleasant or intolerable to the subject or patient receiving TMS, the TMS operator, or other persons in the vicinity of the TMS device. Intolerance may be particularly pronounced for persons with increased sensitivity to noise (hyperacusis). Hyperacusis is estimated to affect 8-15% of the general population [Baguley, D. M. (2003). Hyperacusis. Journal of the Royal Society of Medicine, 96(12): 582-585; Coelho C. B., Sanchez T. G., and Tyler R. S. (2007). Hyperacusis, sound annoyance, and loudness hypersensitivity in children. Progress in brain research 166:169-178.] and has a higher prevalence in patients with some psychiatric and neurological disorders, including tinnitus, migraine, autism spectrum disorder, depression, and post-traumatic stress disorder as well as other anxiety disorders. For these disorders, TMS is either approved (depression) or investigated as a therapeutic intervention. Furthermore, tension-type headache is the most common side effect of rTMS, occurring in 23%-58% of subjects or patients and in 16%-55% of those receiving sham [Loo C. K., McFarcluhar T. F., and Mitchell P. B. (2008). A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. International Journal of Neuropsychopharmacology, 11(1):131-147; Machii K., Cohen D., Ramos-Estebanez C., and Pascual-Leone A. (2006). Safety of rTMS to non-motor cortical areas in healthy participants and patients. Clinical Neurophysiology, 117(2):455-471; Janicak P. G., O'Reardon J. P., Sampson S. M., Husain M. M., Lisanby S. H., Rado T. J., Heart K. L., and Demitrack M. A. (2008). Transcranial magnetic stimulation in the treatment of major depressive disorder: A comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. Journal of Clinical Psychiatry, 69(2):222-232.]. Since tension-type headache can be triggered by exposure to noise [Martin P. R., Reece J., and Forsyth M. (2006). Noise as a trigger for headaches: Relationship between exposure and sensitivity. Headache, 46(6):962-972; Wober C. and Wober-Bingol C. (2010). Triggers of migraine and tension-type headache. Handbook of Clinical Neurology, 97:161-172.] it is a distinct possibility that the noise generated by the TMS device is a contributor. Scalp nerve and muscle stimulation and scalp pressure from the coil and other hardware during TMS likely contribute to headache as well (Borckardt et al., 2010; Trevino et al., 2011). However, sham TMS typically reproduces the coil sound but not the scalp stimulation (Maizey et al., 2013). Therefore, the occurrence of headache in sham TMS, in some cases at similar rates as in active TMS (Janicak et al., 2008; Maizey et al., 2013), supports a role of the TMS device noise as a headache trigger. Therefore, in some patient groups, the TMS device noise may present an obstacle to receiving potentially beneficial treatment.
(3) The auditory perception of the TMS sound results in an evoked response in the brain that is not generated by the magnetic stimulus, but is nevertheless synchronous with it. Thus, it is difficult to decouple the effect of the magnetic pulse from the auditory response [Komssi S., and Kahkonen S. (2006). The novelty value of the combined use of electroencephalography and transcranial magnetic stimulation for neuroscience research. Brain Research Reviews, 52(1):183-192.]. This can confound experimental studies and can produce unintended modulation and interaction effects in clinical applications. Repetitive auditory stimulation, for instance, can also induce long term potentiation (LTP) in the brain [Clapp W. C., Kirk I. J., Hamm J. P., Shepherd D., and Teyler T. J. (2005). Induction of LTP in the human auditory cortex by sensory stimulation. European Journal of Neuroscience, 22(5):1135-1140; Clapp W. C., Hamm J. P., Kirk I. J., and Teyler T. J. (2012). Translating Long-Term Potentiation from Animals to Humans: A Novel Method for Noninvasive Assessment of Cortical Plasticity. Biological Psychiatry, 71(6):496-502; Zaehle T., Clapp W. C., Hamm J. P., Meyer M., and Kirk I. J. (2007). Induction of LTP-like changes in human auditory cortex by rapid auditory stimulation: An FMRI study. Restorative Neurology and Neuroscience, 25 (3-4):251-259.], which overlays the modulation effect in rTMS. For example, one of the FDA-approved rTMS depression paradigms uses 10 Hz pulse trains, which corresponds to the frequency range of highest auditory cortex sensitivity (10-14 Hz) and is close to the frequency at which auditory-induced LTP has been demonstrated in humans (13 Hz, see [Clapp W. C., Hamm J. P., Kirk I. J., and Teyler T. J. (2012). Translating Long-Term Potentiation from Animals to Humans: A Novel Method for Noninvasive Assessment of Cortical Plasticity. Biological Psychiatry, 71(6):496-502.]
(4) The loud noise generated by TMS devices presents challenges to the environment where the TMS device is located and operated. Since the sound of the TMS device may penetrate neighboring rooms in the building, researchers and physicians using TMS devices face challenges from other occupants and/or the management of the building where the device is located. Moreover, in many countries, noise emission is restricted by regulations. Since many medical offices are not located in designated industrial areas, emission limits as strict as 55 dB(A) outside and 35 dB(A) in neighboring units within the building can apply [TAL (1998), German Technical Instruction on Noise Protection According to the Federal Control of Pollution Act BlmSchG/Technische Anleitung zum Schutz gegen Lärm erlassen auf der Basis des Bundesimmissionsschutzgesetzes. GMBI No. 26/1998, p. 503.]. Without enhanced noise abatement measures in the building, the use of TMS for medical purposes may be restricted.
Many of these considerations apply to devices for peripheral magnetic stimulation as well. Therefore, the principles of this invention are applicable to peripheral magnetic stimulation devices as well.
State-of-the-Art Approaches to Low Noise TMS
To reduce the noise generated by the TMS device, some manufacturers use techniques to dampen oscillations in the stimulation coil. The effectiveness of this approach has been limited, as evidenced by the high noise level of commercially available devices [Starck J., Rimpilainen I., Pyykko I, and Toppila E. (1996). The noise level in magnetic stimulation. Scandinavian Audiology, 25(4): 223-226; Counter S. A., Borg E. (1992) Analysis of the coil generated impulse noise in extracranial magnetic stimulation. Electroencephalography and Clinical Neurophysiology, 85(4):280-288.]. A proposed approach for more drastic noise reduction involves placing the coil winding in an evacuated vessel [Ilmoniemi R. J. et al. (1997). EP 1042032, WO 99/27995]. That approach attempts to minimize the acoustic emission by omitting all media for sound transmission around the coil winding. This approach, however, has a number of shortcomings: (1) The air-tight, evacuated vessel around the coil could increase the spacing between the coil winding and the stimulation target thus worsening the electromagnetic coupling to the target and, hence, the electrical efficiency of the system. (2) There would be alternative noise conduction paths from the points where the coil conductor enters the evacuated vessel, from the coil cable, and from the pulse generator. (3) The evacuated vessel system would be large, inflexible, impractical, potentially fragile, and expensive.
Therefore, there is a compelling need for the development of TMS devices that generate less noise since existing or proposed TMS systems do not offer adequate solution to the problem. Addressing this need, the invention proposes the concept of a quiet TMS technology that could substantially reduce the noise generated by TMS.